RENAL ALLOGRAFT REJECTION. LESSONS FROM ULTRASTRUCTURAL OBSERVATIONS

 

B. Ivanyi

Department of Pathology, University of Szeged, Szeged, Hungary

 

 

Electron microscopy is an appropriate tool with which to describe changes in renal capillaries, and to recognize contact-dependent cellular cytotoxicity.

1) Acute cellular rejection. Peritubular capillary (PC) endothelial cells undergo high-endothelial venule-like transformation, characterized by endothelial hypertrophy, and by the increased adherence and transcapillary passage of lymphocytes and monocytes. Cytotoxic lymphocytes cause the lysis of endothelial cells. Tubular-wall localized cytotoxic lymphocytes induce the detachment of epithelial cells from the basement membrane, and mediate the lysis/apoptosis of epithelial cells.

2) Acute humoral rejection. Different patterns of PC endothelial cell damage may be seen, such as an increased occurrence of apoptosis, lysis, fragmentation in the vicinity of inflammatory cells, swelling and/or detachment from the PC basement membrane. Prolonged or repeated alloimmune injury leads to the multiplication of the PC basement membrane.

3) Chronic rejection (CR). The PCs exhibit circumferential multiplication of the basement membrane. Transplant capillaropathy (5 or more layers in at least 3 PCs, or 1 PC with 7 or more layers) is the most sensitive marker (above 80%) of CR. Electron microscopy verifies transplant glomerulopathy (duplication of the glomerular basement membrane) more precisely than light microscopy does. The ultrastructural verification of transplant capillaropathy and/or transplant glomerulopathy (cumulative incidence above 90%) doubles the frequency of the diagnosis of CR and markedly reduces that of chronic transplant nephropathy.

4) Pathogenesis of CR. Not completely understood. In 64 cases of CR (presence of rejection markers: transplant arteriopathy and/or transplant glomerulopathy and/or transplant capillaropathy), the PCs in 25 cases (40%) displayed immunostaining with complement 4d, indicating that ongoing humoral rejection plays a role in the evolution of CR in a subset of cases (unpublished; in collaboration with H. Regele and M. Exner, Vienna, Austria). 5) 5) 5) Comparison of rat model of CR to human CR. Alterations in Fisher kidneys implanted into Lewis rats have been widely regarded as a model of CR, characterized by proteinuria, focal-segmental glomerulosclerosis, patchy interstitial fibrosis and tubular atrophy. Since markers of CR and signs of T-cell mediated cytotoxicity could not be observed in the animals, a chronic-active alloimmune injury to the graft vasculature does not seem to be involved in the rat model. The lesions resembled glomerular hyperfiltration injury, and thus the model corresponds to focal-segmental glomerulopathy rather than the CR (unpublished; in collaboration with P. Hamar, Budapest, Hungary).

 

Supported by grant OTKA T-038271 (Budapest, Hungary) to B. I.


RENAL ALLOGRAFT REJECTION. LESSONS FROM ULTRASTRUCTURAL OBSERVATIONS

 

B. Ivanyi

Department of Pathology, University of Szeged, Szeged, Hungary

 

Mailing address: Dr. Bela Ivanyi

Department of Pathology

H-6720 Szeged, Allomas u. 2

Hungary

 

ivanyi@patho.szote.u-szeged.hu